ROLE OF NITRIC-OXIDE IN THE CONTROL OF APOPTOSIS IN THE MICROVASCULATURE

Cell death occurs by either apoptosis or necrosis. Apoptosis is a cell ular event in which a sequence of biochemical and morphological change s conclude in the death of the cell. Apoptosis is an important mechani sm to control the number of cells and maintain tissue architecture. Ni tric oxide (NO) is a multifunctional molecule that is synthesized by a family of enzymes, namely nitric oxide synthases (NOS). NO is implica ted in several physiological functions within the microvascular enviro nment, i.e. regulation of vascular tone, antiplatelet and antileukocyt e properties and modulation of cell growth. Several investigations hav e demonstrated effects of NO on gene transcription. In this regard, NO has been also implicated in the apoptotic processes. The goal of the present review is to summarize the current knowledge about the relatio nship between NO and different genes involved in the apoptotic phenome na with focus in the cells of the microvascular environment, i.e. mono cytes/macrophages, endothelium and vascular smooth muscle cells. Diffe rent studies have revealed that stimulation and inhibition of differen t genes are required to stimulate apoptosis. NO modulates the expressi on of bcl-2 family members, p53, interleukin-1 beta-converting enzyme family proteases and the cytokine receptor Fas. Therefore, NO generate d from NO donors or synthesized by NOS induces cell death via apoptosi s in a variety of different cell types. On the other hand, in the endo thelial cells NO seems to have a relevant role in the maintenance of t he confluent endothelial monolayer inhibiting apoptotic-related mechan isms. Furthermore, the redox states of the cells play an important rol e in the effects of NO as promotor of apoptosis. There have been excit ing advances in the understanding of the molecular relationship betwee n apoptosis and NO. Therefore, NO could be an important mediator to co nsider in the context of future therapeutic applications particularly considering apoptosis as a mechanism to maintain vascular architecture . (C) 1998 Elsevier Science Ltd. All rights reserved.